Stable fitness during COVID-19: Results of serial testing in a cohort of youth with heart disease

Background Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease (HD). Methods A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition via bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired t-test. Results There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2–25.9 ± 9.1 kg, p < 0.0001), weight (58.7 ± 21.5–63.9 ± 22 kg, p < 0.0001), and body fat percentage (22.7 ± 9.4–24.7 ± 10.4%, p = 0.04). The results were similar when stratified by age <18 years old (n = 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO2 increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO2. There remained no difference in predicted peak VO2 when excluding patients with pre-existing activity restrictions (n = 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings. Conclusions The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.


Introduction
Concerns about cardiac damage following coronavirus disease 2019 (COVID-19) and society-wide mitigation strategies disrupted children's lives during the COVID-19 pandemic, particularly during the early stages. Policies, such as school and sport restriction, dramatically altered daily routines, leading to more school-based and leisure screen time and less time in active play with their peers (1). Decreased physical activity because of COVID-19 related restrictions has been shown in multiple studies in pediatrics (1)(2)(3). Little is known about the effect this has had on fitness and body composition in pediatric and congenital heart disease (CHD), individuals who are often already deconditioned. The only known pediatric CHD study included a combination of individuals with and without heart disease, reporting a decline in peak oxygen consumption (VO 2 ) on serial exercise testing performed during the pandemic (4).The aims of this study were to: (1) understand how COVID-19 mitigation strategies affected fitness and also body composition in youth with heart disease, and (2) determine if children with heart disease and pre-existing exercise restrictions were more likely to have alterations in their fitness or body composition compared to without such restriction.

Materials and methods
This study was approved by the Cincinnati Children's Hospital Medical Center Institutional Review Board, and informed consent was not required for this study.

Patients
We identified all individuals with heart disease ≤21 years old at the time of the first test, and who underwent a routine cardiopulmonary exercise test (CPET) at Cincinnati Children's Hospital within a year before and after March 21, 2020 (i.e., the date that extensive COVID-19 mitigation strategies including school and sports cancellations were established locally). This group we defined as the "COVID lockdown" study group. Heart disease was defined as either electrocardiographic (i.e., Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia) or CHD (bicuspid aortic valve, Fontan physiology, etc). We included only those for whom exercise testing was performed as routine standard of care and not secondary to cardiac symptoms or concern for deterioration (i.e., testing to assess for adequate beta-blockade if long QT patients, evaluate for serial changes in peak VO 2 in CHD patients for prognostic purposes, ST segment/T wave changes in patients with left ventricular outflow tract obstruction). This was evaluated on chart review utilizing the electronic medical record. Additional exclusion criteria included a submaximal test (details below) and missing data. Additionally, to determine if any changes in fitness were secondary to COVID-19 mitigation or rather typical fitness changes in patients with heart disease, an age, sex, and diagnosismatched historical control group was performed for those with serial CPET performed during the 3 years prior to the COVID-19 pandemic. To help account for other confounders, following initial result reporting a sensitivity analysis was performed to evaluate for differences in serial testing by excluding patients with pre-existing activity restrictions, adult patients, and those with a percent predicted peak VO 2 < 80%. Lastly, all patients tested during the COVID-19 pandemic required a negative PCR test on a nasopharyngeal swab prior to their CPET.

Study measures 2.2.1. Baseline data
We extracted demographic and other baseline data from the electronic medical record including age, sex, height, weight, race, medications, cardiac pacemaker, and documented sport restrictions.

Bioimpedance assessment
Anthropometric data were measured by Bioimpedance assessment (BIA) (InBody370; InBody, Cerritos, CA, United States) immediately before the CPET, as previously described (5). Bioelectrical impedance analysis (BIA) is part of our local standard of care prior to CPET and is an alternative approach to measure body composition with good agreement to dual energy x-ray absorptiometry (6, 7).

CPET
Exercise testing was performed on a stationary cycle ergometer (Corival; Lode; Groningen, The Netherlands) with an individualized incremental ramp protocol. The rate of increase was chosen by experienced clinical exercise physiologists based on the patient's body size and expected fitness, targeting an exercise duration of approximately 10 min. Cardiopulmonary responses to exercise were assessed breath-by-breath (Ultima CardiO2; MGC Diagnostics; Saint Paul, MN, United States). Criteria for a maximal effort exercise test were that 2 of the following 3 criteria were met: respiratory exchange ratio >1.10; maximal heart rate greater >85% of the age-predicted maximum (220 -age in years); or maximal Rating of Perceived Exertion ≥18 on a 6-20 scale (8). Predicted peak VO 2 was calculated per Wasserman et al. and Cooper et al. (9,10). In adult patients with a body mass index (BMI) <18 and >25, the underweight and overweight regression equations were used, respectively (9).

Statistics
Descriptive normally distributed data are presented as mean ± standard deviation. Differences between serial tests for both the COVID-19 lockdown and historical control groups were assessed using a paired t-test. To determine if there was a difference in the baseline fitness testing of both the control and COVID groups, a 2-sided t-test was performed with each group's initial CPET results. All presented p-values are two-tailed (where applicable) and differences and associations were considered significant when p < 0.05. Statistical analyses were performed using JMP ® , Version 15 (SAS Institute Inc., Cary, NC).

Results
There were a total of 48 patients who underwent serial testing, with the first test performed within 12 months before and the second test performed within 12 months after the COVID-19 lockdown. There were 15 patients excluded (6 tested because of concern for clinical decompensation, 6 submaximal effort tests, 3 missing data). There were 33 remaining patients (mean age 15.3 ± 3.4 years at the time of the first test; 46% male) who were included in the analysis. Underlying cardiac diagnoses are presented in Table 1. Primary diagnosis was related to electrophysiologic disease in 18 patients, while 15 had structural heart disease. Of note, 36% (12/33) were restricted from sports before COVID-19 with the reason for sports restriction being concern about ventricular arrhythmia in 10 patients and severe left ventricular outflow tract obstruction in 2 patients. In the COVID group, 58% (19/33) were prescribed beta-blockers. None had a cardiac pacemaker, had medication changes, or experienced unexpected arrhythmias during the test.
There was no significant difference in sport restriction and beta-blocker usage between the post COVID-19 lockdown and historical control groups. No patients were diagnosed with COVID-19 prior to their exercise test.
When comparing with the cohort that had testing in the years prior to the COVID-19 pandemic (historical control) (N = 65; mean age 14.9 ± 3.3 years at the first test; 49% male), there was no difference in the sex, diagnoses, age, or size between groups. On comparing baseline CPET results between the COVID-19 lockdown and historical control groups, there were no significant differences in any of the CPET parameters studied. In the historical control group, there was no significant change in absolute peak VO 2 (1,826.8 ± 696.8-1,866.7 ± 655.6 ml/min,   Table S1).
Results were similar after excluding the 7 patients in the COVID lockdown group who were >18 years old at the initial test (Supplementary Table S2). The 7 patients >18 years old had a significant decrease in total work (221.4 ± 47.1-207.3 ± 49.4 watts, p = 0.04), but there was no change in other CPET variables. When removing patients with a peak VO 2 < 80%, there remained no difference in percent predicted peak VO 2 in those with more normal fitness (89.6 ± 11.2 vs. 89.3 ± 16.4, p = 0.9). Lastly, the groups with a primary electrophysiologic diagnosis were also similar to those with a structural heart disease diagnosis in terms of change in percent predicted peak VO 2 .

Discussion
Findings from this observational study revealed no significant change in the aerobic capacity or body composition, beyond those associated with puberty, from before to after the COVID-19 pandemic and related societal lockdown. This is notable, as there has previously been concern that COVID mitigation could affect exercise habits in this population (1,11). There were no differences in fitness when comparing serial testing separated by either sex, activity restriction, or in the matched paired historical control group. There were changes in body composition seen between tests, but this was likely secondary to normal pubertal maturation in a largely pediatric cohort.
There have been reports of decreased physical activity related to COVID-19 mitigation strategies both in healthy Data are presented as mean ± SD. A paired t-test was performed to determine differences between paired data. A p-value < 0.05 was considered significant. cm, centimeters; kg, kilogram; m, meters; BMI, body mass index; SMM, skeletal muscle mass; HR, heart rate; VO 2 , oxygen consumption; % pred, percent predicted; VAT, ventilatory anaerobic threshold; SBP, systolic blood pressure; SpO 2 , oxygen saturation measured via pulse oximeter; VE/VCO 2 slope, minute ventilation/carbon dioxide production slope.
Powell et al. 10.3389/fped.2023.1088972 Frontiers in Pediatrics children and in those with heart disease (1,11). Whether or not our cohort engaged in less physical activity is unknown, but their objective measures of fitness did not change, which is the opposite of what was reported by Burstein DS et al. (4). This may mean many of the patients were already deconditioned at the time of the initial CPET, as evidenced by an average peak VO 2 of ∼78% of predicted, compared to ∼96% in the Burstein DS et al. cohort (4). Additionally, the lack of change in fitness may be secondary to pre-existing activity restrictions applied by the patients' medical teams, although the lack of change in VO 2 in those not activity restricted argues against this. Lastly, this may mean that the introduction of lockdown measures did not alter their physical activity as they were already sedentary and deconditioned, which is not unusual for a typical congenital heart disease cohort. Prior to COVID-19, youth with congenital heart disease were shown to be more sedentary than their peers (12,13). Thus, the introduction of lockdown measures may not have resulted in a significant change in their physical activity levels. This is further supported by the lack of change in the already low peak VO 2 on serial testing in the pre-COVID control group. This study continues to highlight the need to encourage physical activity in youth with congenital heart disease. While the absence of direct negative effects from the lockdown on fitness in children with heart disease is reassuring, this population, both in our cohort and others, has been shown to be significantly deconditioned (14)(15)(16). This is meaningful, since decreased peak VO 2 has both negative prognostic and functional implications (17)(18)(19). Recreational and competitive activities should be encouraged in this population with an eye towards the risk: benefit calculation, balancing the concerns for sudden cardiac arrest during athletics, and the long-term morbidity and mortality that arises from sedentary behaviors. For individuals so severely deconditioned that participation in organized sports would be impractical, exercise prescription and structured cardiac rehabilitation should be encouraged to improve cardiopulmonary fitness (20).
While this study focused on evaluating the effect of COVID-19 mitigation strategies on the body composition of children and young adults with heart disease, body composition changed during the study period in a pattern that is likely consistent with normal pubertal changes (21). Increase in both skeletal muscle mass and body fat percentage results in an increase in total weight in a pubertal population, which was seen in our cohort. The increase in the total weight for the males was largely driven by increases in skeletal muscle mass while the increase in weight for the females was largely due to increased adiposity; this is in keeping with typical sex-specific pubertal body composition changes (21). These changes remained when the 7 patients older than 18 years-old were removed from the analysis, again supporting expected somatic growth as the likely explanation. The lack of significant change in predicted peak VO 2 in this cohort further supports that these body composition changes were most likely related to normal, expected growth. Unfortunately, secondary to the retrospective design of this study we do not have specific information on the exact pubertal stage of these patients. This should be taken into account for future pediatric studies involving serial body composition measurements.
There were other limitations to this analysis. The available sample size limits statistical power, and a subset of the null findings may represent false negative findings, particularly those with a small effect size. The comparison group lacked body composition data, as the InBody Bioimpedance scale was not widely used in our laboratory until early 2019; thus it is unknown if the changes in body composition in the study cohort is reproduced in the age, sex, and diagnosis-matched cohort. Additionally, questions on specific exercise habits and sports participation are not routinely asked by all of the providers in our hospital. Additional sampling bias may also exist secondary to the retrospective design of the study.

Conclusion
The COVID-19 pandemic and related lifestyle changes do not appear to have had an substantial negative impact on aerobic fitness in children and young adults with heart disease. While this is largely reassuring, these finding may be in part related to pre-existing chronic deconditioning, pre-limited participation in organized sport, or sampling bias.

Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement
The studies involving human participants were reviewed and approved by Cincinnati Children's Hospital IRB. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements. Written informed consent was not obtained from the minor(s)' legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

Funding
Drs Powell and Opotowsky were supported by the Cincinnati Children's Hospital Heart Institute Research Core (HIRC).